The over-all research objective of this Program-Project is a better understanding of the physiologic mechanisms of hemostasis, of the pathologic derangements of these mechanisms that result in hemorrhagic or thrombotic diseases, and the development of therapeutic tools to combat these disorders. A multi-directional approach is being employed which includes such studies on the plasma coagulation factors as the genetic physiologic mechanisms that control their production, sites of formation at organ, tissue, cellular, and molecular levels; the biochemical properties and reactions of specific factors, e.g., antihemophilic factor and fibrin-stabilizing factor; the purification and testing of plasma fractions in the development of therapeutic preparations; a comparative study of the clotting and cellular agglutination processes of human and synthetic inhibitors to further study of the complex coagulation reactions, and continued attack at the ultrastructural level on the cellular reactions that lead to intravascular agglutinates and clots.